The Nexus of Iron, Senescence, and Fibrosis in Endometriosis: A Narrative Review

Endometriosis is a prevalent chronic inflammatory condition impacting 5-10% of reproductive-age women, commonly resulting in debilitating pelvic pain and infertility. Despite extensive research efforts, the precise underlying pathophysiology remains largely unclear. Emerging evidence increasingly suggests that cellular senescence, iron overload, and fibrosis collectively form a critical pathological axis that significantly contributes to the persistence and severity of the disease. However, the intricate mechanistic interplay between the immune system's failure to effectively clear senescent cells, the damaging effects of iron-induced oxidative stress, and the subsequent fibrotic remodelling is still poorly understood. This narrative review highlights the interconnected roles of impaired immune clearance of senescent cells, iron accumulation, and fibrosis development in driving endometriosis pathogenesis. The review aims to clarify how iron overload and cellular senescence contribute to the progression of endometriosis. It also evaluates novel therapeutic strategies that target iron dysregulation and senescence pathways. By exploring this detrimental triad, we seek to identify potential new avenues for transforming the management of endometriosis, offering hope for more effective treatments to alleviate the significant burden on affected women.